Mice have become the primary model for the study of ocular diseases in humans. Because mice and humans share about 95% of their genome, a given gene in a mouse will likely have a homologous chromosomal segment in humans. Moreover, using mice for genetic research is advantageous because, for example, genetically identical mice can be inbred, disease progression in mice is more rapid due to their short life span, and mice are readily available for examination. Because of these advantages, mouse models are expected to play a vital role in the development of new pharmaceutical therapies for glaucoma, retinal degeneration, and retinal vascular diseases.
In vivo quantitative and qualitative assessment of retinal morphology and anatomy in mice, is a necessary fundamental step to characterize the various ocular disease phenotypes, track disease progression, or evaluated disease therapies. Traditional approaches to imaging the interior portion of the mouse eye, known as the fundus, have proven to be tedious. One commercial technique of imaging the mouse eye relied upon a blind technique, wherein the operator fired a small camera multiple times at the mouse eye, without being able to see the image or assurance that a clear image was produced. Another alternative was to use two operators, one to hold the mouse and another to operate the camera, but this technique often produced inferior quality images.
Presently, optical coherence tomography (OCT) is a recognized technique for rapid real-time evaluation of retinal morphology in live mouse. OCT can provide a high-resolution, cross-sectional image of the retinal microstructure. However, there are several challenges with OCT in accurately and effectively imaging the interior surface of the fundus. For example, the length of a mouse eye is approximately ⅛ the size of a human eye, making image capture more difficult. Additionally, mice do not voluntarily agree to be fixated for a retinal examination, making it difficult to align the imaging device to the precise ocular position. Moreover, the eye of a mouse dehydrates very rapidly, requiring researchers to make rapid image acquisitions.
One solution to the alignment problem presented by mouse OCT imaging is to obtain a real-time image of the mouse eye and fundus, which would make it possible to visualize to the OCT area of analysis to control the OCT scan position. Accordingly, several techniques have been developed to acquire fundus images of the mouse eye, such as using a small animal fundus camera with a lens, or using human fundus camera or a slit-lamp with a lens.
Slit-lamps combined with OCT imaging have been shown to produce fast and reliable images of the mouse fundus. Slit-lamp bio-microscopes provide a flexible design platform suitable for many varieties of small animals. However, slit-lamps themselves are often large, complex, and difficult to align for small animals. Moreover, slit-lamps traditionally employ an incandescent white light source to illuminate the fundus, which are often large and require a high current to operate. As such, a need exists for a compact table-top combined fundus camera and OCT imaging system for live mice that records and images rapidly and accurately.